Cross-sectional association of soluble thrombomodulin with mild peripheralartery disease; the ARIC study

Thrombomodulin, an endothelial membrane glycoprotein, is an essential part of the protein C anti-coagulant pathway. It may also have a role in the reg ulation of fibrinolysis. We carried out a cross-sectional study to assess t he association of soluble thrombomodulin (sTM) with peripheral artery disea se (PAD) in a stratified random sample (n = 863) of otherwise healthy black and white participants of the Atherosclerosis Risk in Communities (ARIC) S tudy. PAD was more common in black than in white participants and associate d with classical risk factors in an expected manner; positively with age, s moking, hypertension, diabetes (P = 0.05), and LDL-cholesterol, and inverse ly with HDL-cholesterol. Significant positive associations were observed al so with fibrinogen and white blood cell count. Overall, the sTM concentrati on was not a significant predictor of PAD. The association was, however, mo dified by the level of factor VIII:C in whites (P = 0.002 for the interacti on), but not in blacks. Protein C was inversely associated with PAD prevale nce (odds ratio 0.33, 95% CI 0.18-0.61, P = 0.0004). sTM was inversely asso ciated with plasminogen, but no associations with t-PA, PAI-1, Or D-dimer w ere seen. In conclusion, the present results provide some additional eviden ce on the role of thrombomodulin-protein C pathway in atherosclerotic disea se and support our earlier observation on interaction between sTM and facto r VIII:C. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.